effects of estrogen receptor gene-alpha polymorphism on bone mineral density and serum osteoprotegerin levels in postmenopausal Egyptian women

The gene coding for estrogen receptor-alpha [ER-a] is a potential candidate for the regulation of bone mineral density [BMD] in postmenopausal women. The present study was aimed at elucidating the role of two restriction fragment lengths Pvu II and Xba I polymorphisms of the ER-a gene as determinants of bone mineral density; special attention was paid to the correlation between serum osteoprotegerin [OPG] levels and BMD in different ER-a genotypes in postmenopausal [PM] Egyptian women. BMD was measured at the femur neck [FN-BMD]. ER-a gene polymorphisms were detected by PCR-RFLP. Serum OPG levels were measured by an enzyme linked immunosorbent assay. There were significant differences in BMD and OPG according to different genotypes of Pvu II Single-nucleotide polymorphism [SNP]. Carriers of the pp genotype were more likely to have lower BMD and lower OPG values than noncarriers. While there was no significant relationship between Xbal polymorphism and these variables. Postmenopausal [PM] women were stratified into; those with osteoporosis and those without osteoporosis. The difference in BMD and OPG among genotypes were significant in PM with osteoporosis. Further we confirmed that the frequency of p allele. and pp genotype of Pvu II polymorphism were significantly higher in PM with osteoporosis as compared to PMwithout osteoporosis. Xba I failed to show any significant difference in genotype and allele frequencies between the two groups. Genotypes modulate the relationships between BMD and OPG levels, in women with the PP [r=0.512, p<0.000l] and Pp [r=0.346, p<0.0009] genotypes but not in women with the other genotypes [p>0.05]. These results suggest that the Pvu II polymorphism of ER-a may be associated with the FN-BMD in PM Egyptian women. Further, P allele carriers supposed to protect against PM osteoporosis at least partly by increasing serum OPG

Multi-drug resistance 1 genetic polymorphisms gene expression and prediction of chemotherapy response in breast cancer Egyptian patients

Although anthracycline-based chemotherapy is a crucial treatment for breast cancer, its outcome is limited by the multidrug resistance MDR. Overexpression of P-glycoprotein [Pgp] a transmembrane active efflux transporter of various drugs and carcinogenic substrate, may result in MDR. The impact of MDR1 polymorphisms on MDR1 expression and risk of breast cancer, and whether it can alter chemotherapeutic agents response in breast cancer is unclear. The present work studied the relevance between MDR1 C3435T, C1236T, G2677T/A polymorphisms and MDR1 gene expression and susceptibility to breast carcinoma as well as sensitivity to anthracyine-based chemotherapy in Egyptian females with breast cancer [BC]. We determined mRNA levels of MDR1 in breast tumor specimens [n=190] by real-time rt-PCR. Blood samples from BC female patients and healthy controls were obtained for genotyping. ARMS-PCR assay was used for detection of C3435T, C1236T and G2677T/A Polymorphisms. This study revealed that C3435 TT patients showed a significant decrease in MDR1 mRNA level compared -with CC genotypes. No association was found between the MDR1 C1236T, G2677T/A polymorphisms and MDR1 mRNA expression. The frequency of C3435 TT genotype and T allele were significantlyhigher in BC patients compared to the controls [P < 0.05]. C3435 TT and C3435 CT had odds ratio [p-value] 5.6 [0.001] and 2.28 [0.01] for response to anthracycline-based chemotherapy, respectively, compared to CC genotype. No statistically significant differences were observed between patients and control regarding the allelic and genotypic frequencies of MDR1 C1236T, G2677T/A polymorphisms as well as no correlation was detected to the response rate to anthracycline-based chemotherapy. Our results suggested that C3435T, but not C1236T or G2677T/A, was associated with changes in MDR1 gene expression and hence alters the response after anthracyclin based chemotherapy